The goal of this project it to better understand the natural history of Lyme disease and possible causes for persisting symptoms. We plan to develop reliable objective markers of infection, of clinical status and of host responses to the organism in order to discern the scope and the implications of persistent borrelial infection, the effectiveness of current treatment options, and the development of new therapeutics approaches. For that, a clinical protocol was developed and has been aproved by the NIAID IRB. The study will assemble a well characterized cohort of patients with presumed chronic Lyme disease and relevant controls. These patients will be extensively evaluated in a cross-sectional study and the neuroborreliosis patients will be followed prospectively after therapy with intravenous ceftriaxone. Research techniques include PCR, serologic and antigen capture assays, neuroimaging, cytokine and lymphocyte proliferation studies, mass spectroscopy for measurement of inflammatory indicators in spinal fluid and neuropsychologic and andiologic investigations. These studies will yield a prospective database upon which stringent diagnostic criteria can be established and future therapeutic trials can be designed.